Sequential high-dose methotrexate and cytarabine administration improves outcomes in real-world patients with primary central nervous system lymphoma: A report from the Australasian Lymphoma Alliance.

Autor: Tatarczuch M; Monash Haematology, Monash Health Centre Melbourne Victoria Australia.; School of Clinical Sciences Monash University Melbourne Victoria Australia., Lewis KL; Department of Haematology Sir Charles Gairdner Hospital Perth Western Australia Australia.; Linear Clinical Research Nedlands Western Australia Australia., Gunjur A; Department of Oncology Austin Health Melbourne Victoria Australia., Shaw B; Monash Haematology, Monash Health Centre Melbourne Victoria Australia., Poon LM; National Cancer Institute Singapore Singapore.; Department of Haematology National University of Singapore Singapore Singapore., Paul E; Department of Haematology St. Vincent's Hospital Melbourne Victoria Australia., Ku M; Department of Haematology St. Vincent's Hospital Melbourne Victoria Australia.; University of Melbourne Melbourne Victoria Australia., Wong M; Department of Haematology Gold Coast University Hospital Southport Queensland Australia., Ai S; Department of Haematology St George Hospital Kogarah New South Wales Australia., Beekman A; Department of Haematology University Hospital Geelong Geelong Victoria Australia., Ciaccio PRD; Department of Haematology St. Vincent's Hospital Sydney New South Wales Australia.; College of Health and Medicine Australian National University Canberra Australia., Krigstein M; Department of Haematology St. Vincent's Hospital Sydney New South Wales Australia., Wight J; Department of Haematology and Bone Marrow Transplantation Townsville University Hospital Douglas Queensland Australia., Coombes C; College of Health and Medicine Australian National University Canberra Australia.; Department of Haematology The Canberra Hospital Garran Australian Capital Territory Australia., Gilbertson M; Monash Haematology, Monash Health Centre Melbourne Victoria Australia.; School of Clinical Sciences Monash University Melbourne Victoria Australia., Tey A; Pharmacy Department Monash Health Melbourne Victoria Australia., Shortt J; Monash Haematology, Monash Health Centre Melbourne Victoria Australia.; School of Clinical Sciences Monash University Melbourne Victoria Australia., Nagarajan C; SingHealth, Duke-NUS Blood Cancer Centre Singapore Singapore.; Department of Haematology Singapore General Hospital Singapore Singapore., Talaulikar D; College of Health and Medicine Australian National University Canberra Australia.; Department of Haematology The Canberra Hospital Garran Australian Capital Territory Australia., Hamad N; Department of Haematology St. Vincent's Hospital Sydney New South Wales Australia.; School of Clinical Medicine Faculty of Medicine and Health University of New South Wales Sydney New South Wales Australia.; School of Medicine University of Notre Dame Sydney New South Wales Australia., Ratnasingam S; Department of Haematology University Hospital Geelong Geelong Victoria Australia., Ho SJ; Department of Haematology St George Hospital Kogarah New South Wales Australia.; University of New South Wales Sydney Victoria Australia., Cochrane T; Department of Haematology Gold Coast University Hospital Southport Queensland Australia.; School of Medicine and Dentistry Griffith University Southport Queensland Australia., Hawkes EA; Olivia Newton John Cancer Research Institute at Austin Health Melbourne Victoria Australia.; School of Public Health and Preventive Medicine Monash University Melbourne Victoria Australia., Cheah CY; Department of Haematology Sir Charles Gairdner Hospital Perth Western Australia Australia.; Division of Internal Medicine Medical School University of Western Australia Perth Western Australia Australia., Opat S; Monash Haematology, Monash Health Centre Melbourne Victoria Australia.; School of Clinical Sciences Monash University Melbourne Victoria Australia., Gregory GP; Monash Haematology, Monash Health Centre Melbourne Victoria Australia.; School of Clinical Sciences Monash University Melbourne Victoria Australia.
Jazyk: angličtina
Zdroj: EJHaem [EJHaem] 2024 Jun 21; Vol. 5 (4), pp. 709-720. Date of Electronic Publication: 2024 Jun 21 (Print Publication: 2024).
DOI: 10.1002/jha2.951
Abstrakt: Background: Despite recent advances, optimal therapeutic approaches applicable to subpopulations with primary central nervous system (CNS) lymphoma outside of clinical trials remain to be determined.
Methods: We performed a retrospective study of immunocompetent, adult patients with histologically confirmed diffuse large B-cell lymphoma of the CNS (PCNSL). 190/204 (93%) patients (median age: 65) received one of five high-dose methotrexate (HD-MTX) containing chemotherapy regimens: MPV/Ara-C (HD-MTX, procarbazine, and vincristine, followed by cytarabine [Ara-C]) ( n  = 94, 50%), MATRix (HD-MTX, Ara-C, thiotepa, and rituximab) ( n  = 19, 10%), HD-MTX/Ara-C ( n  = 31, 16%), HD-MTX monotherapy ( n  = 35, 18%) and MBVP (HD-MTX, carmustine, teniposide, prednisolone) ( n  = 11, 6%).
Results: Cumulative median HD-MTX and Ara-C doses were 17 g/m 2 (range: 1-64 g/m 2 ) and 12 g/m 2 (0-32 g/m 2 ) respectively. Using 14 g/m 2 as the reference dose, the median HD-MTX relative dose intensity (HD-MTX-RDI) was 1.25 (0.27-4.57) with 84% receiving > 0.75. The overall response rate (ORR) was 72% (complete response: 50%) after completing HD-MTX. At a median follow-up of 3.41 years (0.06-9.42), progression-free survival (PFS) and overall survival (OS) were different between chemotherapy cohorts, with the best outcomes achieved in the MPV/Ara-C cohort (2-year PFS 74%, 2-year OS 82%; p  = 0.0001 and p  = 0.0024 respectively). On multivariate analysis, MPV/Ara-C administration and HD-MTX-RDI > 0.75 were associated with longer PFS and OS.
Conclusion: Sequential, response-adapted approaches can improve outcomes, even in older patients who are ineligible for a high-intensity concurrent chemotherapy approach and do not undergo traditional consolidative strategies.
Competing Interests: Katharine Louise Lewis: Consultancy/Honoraria: Jansen Roche. Trial steering committee: Loxo/Lilly. Advisory: IQVIA and MSD; Pietro R. Di Ciaccio: Honoraria/travel funding: Janssen, Astra Zeneca, and Gilead/Kite; Chan Y. Cheah: Research funding: Beigene. Advisory: Janssen Cilag. Joel Wight: Honoraria: Janssen, MDI, Beigene, MSD, and Abbvie. Travel support: Kite/Gilead. Jake Shortt: Consultancy: BMS, Otsuka, Pfizer, and Astellas. Speaker's Bureau: Mundipharma and Novartis. Research funding: Astex. Dipti Talaulikar: Consultancy/Advisory/Honoraria: Roche, Janssen, Beigene, Novartis, Amgen, Antengene, CSL, EUSA, BMS, and Takeda. Research funding: Roche, Janssen, and Takeda. Tara Cochrane: Research funding: Beigene. Advisory: Janssen Cilag. Eliza A. Hawkes: Consultancy/Advisory: AstraZeneca, Janssen Oncology, Merck Sharpe & Dohme, Gilead Sciences, Bristol Myers Squibb, Novartis, Beigene, Link Healthcare, and Regeneron. Speaker's Bureau: Roche/Genentech, Regeneron, and Abbvie. Research funding: AstraZeneca, Celgene, Merck KGaA, Janssen‐Cilag, Gilead Sciences, Mundipharma, Bristol‐Myers Squibb, and Roche/Genentech. Travel: AstraZeneca.
(© 2024 The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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